More people feel the bite of MRSA bug

Three years ago, Lisa Esolen, MD, an infectious disease specialist in East Stroudsburg, Pa., encountered a high school football player with a scraped knee and a staph infection that was resistant to commonly used antibiotics such as methicillin, penicillin, oxacillin and cephalosporins. The player became her first patient in what would become a mini-epidemic of local athletes infected by community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA).

CA-MRSA cases continued to surface sporadically over the next few years, and not just among athletes, said Dr. Esolen. But the past few months have been the busiest, with more than 50 cases "in every age range and every situation."

Affected patients, who typically come to her as referrals, often have had multiple skin abscesses, she said. Cases have ranged from a toddler with a dozen quarter-sized abscesses on her legs to an 80-year-old woman with 12 abscesses on her abdomen. In these and other cases, no immediate factors, such as exposure to other infected individuals, seem to explain why these otherwise healthy, non-hospitalized individuals got the infections.

Across the country and even worldwide, CA-MRSA cases have spiked since the condition was identified in 1999. While the first cases primarily were found in specific groups, such as athletes, intravenous drug abusers, military members, children in daycare, or prison inmates, cases now have spread to the general population.

The exact number of cases related to CA-MRSA bacteria strains, which are separate from hospital-associated MRSA strains, are not known because physicians are not required to report them to the CDC or their public health departments. However, research published by the CDC earlier this year estimated that about 2 million people in the U.S. may be carriers of a strain of drug-resistant bacteria in their noses.

In another study published in the Aug. 17 New England Journal of Medicine on emergency room visits by individuals with skin and soft tissue infections (SSTIs) at 11 hospitals nationwide, nearly 60% of those cases (with a range of 15% to 74% in the cities) showed infections with CA-MRSA. A recent March 2006 editorial in Annals of Internal Medicine called CA-MRSA "a remarkable epidemic."

"This has gone from something that we essentially never saw five years ago to the single most common cause of skin infection," said Gregory J. Moran, MD, the lead researcher of the ER study and a clinical professor of medicine in the department of emergency medicine and the division of infectious diseases at .at the Olive View- University of California at Los Angeles Medical Center in Sylmar, Calif.

War on CA-MRSA

CA-MRSA is also increasingly finding its way into clinics and hospitals. In October, the CDC issued new management guidelines stating that the emergence of new epidemic strains of CA- MRSA could pose challenges to MRSA control in healthcare settings.

While the bad news is that antibiotic-resistant cases are rising, the good news is that most of these infections—if identified early enough—still can be eliminated with conventional treatment and, when necessary, appropriate antibiotics. However, CA-MRSA still must be guarded against to prevent serious and even fatal conditions, such as necrotizing pneumonia, necrotizing fasciitis and sepsis, according to recent studies.

In the NEJM study, reviews performed by the CDC of CA-MRSA samples from the 11 ERs across the county revealed that one strain belonging to the USA300 group accounted for 97% of the samples. The remaining groups, including USA400, have caused more serious complications.

"That single pulsed-field type [USA300] has now become the predominant cause of infections," Dr. Moran said. "Fortunately, these strains are relatively more susceptible to antibiotics compared to hospital strains."

However, infected patients with this strain might not necessarily need antibiotics. When researchers tested the antibiotic resistance of these MRSA samples, they found that in 57% of cases, physicians had prescribed antibiotics, usually beta-lactam agents such as cephalexin and dicloxacillin, to which the bacteria were resistant.

"When we looked at those patients treated with drugs that were not active against MRSA, we could not find a difference in outcomes," Dr. Moran said. It supports the idea that "many of these patients probably don't need antibiotics" and that the incision and drainage of the abscesses "are still the primary treatment."

There are several antibiotic options. The researchers tested the antibiotic susceptibilities of the MRSA samples and found that 92% were susceptible to tetracycline, 95% to clindamycin and 100% to rifampin and trimethoprim sulfamethoxazole.

"Any of those are reasonable choices," Dr. Moran said. Only 6% were susceptible to erythromycin and 60% to fluoroquinolones.

The study also looked at which patients in the ERs had higher probabilities of having CA-MRSA. Several possible risk factors were examined, such as prior contact with an individual with the same infection, or patients with "spider bites," essentially skin lesions that were not healing.

Past use of antibiotics, history of MRSA infection and close contact with an infected person were "statistically associated with a higher probability" of CA-MRSA, but "none of them were such strong predictors that you could use them to make treatment decisions," Dr. Moran said.

Unlike several years ago, there no longer is a patient group that should automatically be selected over another for treatment. Instead, MRSA is considered when treating skin and soft tissue infections, particularly when abscesses are present. "It appears now that everyone is at risk," he said.

Institutions: the new front

If the new CA-MRSA clones are "sufficiently fit to sustain endemic levels by transmission in the community," the MRSA situation in hospitals, "which still remains out of control in many countries, could potentially become explosive," Hajo Grundmann, MD, of the Centre for Infectious Disease Epidemiology in the Netherlands, said in the Sept. 2, 2006 issue of The Lancet.

To address this, he called for health care authorities to develop "not only surveillance systems that are able to monitor the clonal dynamics of MRSA over wide geographical areas but also to provide the resources for early recognition of MRSA carriers through rapid screening."

In its recently released "Management of Multi-Drug Resistant Organism in Health Care Organizations, 2006," the CDC noted that transmission within hospitals of MRSA strains first described in the community, such as USA300 and USA400, are "being reported with increasing frequency."

The CDC warned that intrinsic virulence characteristics of the CA-MRSA organisms could result in infections that are "similar to or are potentially more severe than traditional health care-associated MRSA among hospitalized patients."

To meet this challenge, "empiric therapy really needs to change," especially for those patients with SSTI who are going to be admitted to a hospital and have a CA-MRSA, said Henry Blumberg, FACP, program director of the division of infectious diseases at Emory University School of Medicine and a hospital epidemiologist with Grady Memorial Hospital in Atlanta.

Patients entering the hospital with severe SSTI "are a bit different than those you are sending home," said Dr. Blumberg. "In those people requiring admission [Grady Memorial has] changed the empiric antibiotic therapy to vancomycin pending results of cultures to cover the high likelihood that the infection is due to CA-MRSA."

But given the potential ramifications of increased vancomycin use, clinicians still should obtain specimens for culture in the hospital so that infections caused by methicillin-susceptible staph infections (MSSA) can be treated with a beta-lactam rather than vancomycin or non-beta-lactam agents, Dr. Blumberg and colleagues noted in a study in the March 2006 Annals of Internal Medicine.

That study demonstrated that USA300 CA-MRSA had emerged as the predominant cause of community-onset SSTI among patients admitted to the hospital; overall MRSA caused 72% of staphylococcal SSTI.

In a separate study published in the March 2006 Clinical Infectious Diseases, the Emory group demonstrated the emergence of CA-MRSA USA300 genotype as a major cause of health care-associated blood stream infections among patients cared for at Grady Memorial Hospital, suggesting that the line between community and healthcare infections due to CA-MRSA is starting to blur.

Franklin Square Hospital Center in Baltimore received a Robert Wood Johnson Foundation grant last summer to research ways to stop transmission of MRSA in hospitals. It is testing an automated technique that uses DNA identification—instead of the traditional culture method—to quickly detect patients entering the intensive care unit or immediate care unit with MRSA.

"The advantage is that you know within two to three hours that someone is positive as opposed to waiting two to three days," said Anthony Sclama, MD, the hospital's vice president for medical affairs. That shorter waiting period means hospitals can take quicker action to stop further transmission.

Stopping the spread

In one of the first studies of the impact of CA-MRSA in outpatient settings, health care providers at Johns Hopkins Hospital in Baltimore found that special precautions should be taken to make sure CA-MRSA is not transmitted to providers themselves through direct contact with patients or surfaces with CA-MRSA. In 2004, two workers contracted CA-MRSA over a two-week period in a busy HIV outpatient clinic.

While no patients were infected, seven out of 36 surfaces tested were found to be positive for CA-MRSA, said Cecilia Johnston, MD, an infectious disease instructor at Johns Hopkins. The hospital instituted safety precautions that included cleaning treatment areas regularly between each visit.

"We don't know how long this organism lives," Dr. Johnston said, but previous research has shown that the hospital-acquired MRSA can live from three days to six months. Providers are now asked to wear gloves and gowns, and care for exposed skin and wounds in designated treatment areas.

Preparing for "superbugs"

One of the main concerns about antibiotic-resistant bacteria is running out of antibiotics to stop them. While a number of antibiotics have been identified to treat CA-MRSA, concerns exist about the "pipelines running dry" for MRSA and other resistant bacteria, said Dr. Blumberg.

"Unless something is done to enhance or further incentivize drug discovery, we're going to be in trouble because the organisms are running much faster and becoming resistant to drugs much faster than we are developing new drugs," he said.

Overall, MRSA—as the "sexy bug" of the moment—has received more attention from drug companies than other multi-drug resistant microbes, said John G. Bartlett, MACP, professor of medicine at Johns Hopkins School of Medicine, and chair of the Infectious Disease Society of America's Antimicrobial Availability Task Force.

However, the "apparent plethora" of available antibiotics for MRSA infections may be "somewhat misleading," Dr. Bartlett's committee has stated. Instead, there is a critical need for "effective antibiotics that can be taken orally" and permit initial therapy for CA-MRSA.

Overall, it takes eight to 10 years to develop any new antibiotic, Dr. Bartlett said. "And the resistance never goes backwards. It always goes forward."

Physicians should offer advice to their patients on ways that they can avoid spreading CA-MRSA, said Gregory J. Moran, MD, of the division of infectious diseases at Olive View-University of California at Los Angeles Medical Center in Sylmar, Calif.

"These strains appear not only to be resistant to antibiotics but actually more aggressive and prone to causing infections in people who come in contact with it," he said.

Here are some other things to keep in mind, according to the CDC and other health providers:

Notify all providers of the existence of earlier treatment related to CA-MRSA.

Promote washing hands often with soap and water or an alcohol-based hand sanitizer.

Gorwitz RJ, Jernigan DB, Powers JH, Jernigan JA, and Participants in the CDC Convened Experts' Meeting on Management of MRSA in the Community. Strategies for clinical management of MRSA in the community: Summary of an experts' meeting convened by the Centers for Disease Control and Prevention. 2006. Available here.

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